Novel X-linked glomerulopathy is associated with a COL4A5 missense mutation in a non-collagenous interruption.
Novel X-linked glomerulopathy is associated with a COL4A5 missense mutation in a non-collagenous interruption.
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DOI：
10.1038/ki.2010.354
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发表时间：
2011-01
影响因子：
19.6
通讯作者：
Schwaderer, Andrew L.
中科院分区：
文献类型：
--
作者：
Becknell, Brian;Zender, Gloria A.;Houston, Ronald;Baker, Peter B.;McBride, Kim L.;Luo, Wentian;Hains, David S.;Borza, Dorin-Bogdan;Schwaderer, Andrew L.
我们报告了一种新的COL 4A 5突变，尽管缺乏与Alport综合征相关的临床和活检结果，但该突变导致男性快速进展为终末期肾病。受影响的雄性动物出现蛋白尿、可变性血尿、早期进展为终末期肾病;肾活检结果包括整体和节段性肾小球硬化、系膜细胞过多和基底膜免疫复合物沉积。COL 4A 5基因座的外显子测序鉴定了核苷酸665处的胸腺嘧啶至鸟嘌呤颠换，导致密码子222处的苯丙氨酸至半胱氨酸错义突变。该突变在4名男性和4名女性携带者中得到证实，但在6名无症状男性家庭成员和198名无关个体中缺失。受累雄性动物肾活检中的α5（IV）胶原染色正常。222位的苯丙氨酸在脊椎动物中是100%保守的。这是第一次描述与严重肾脏疾病相关的非胶原中断突变，为这种结构基序的重要性提供了证据。与COL 4A 5突变相关的表型范围比以前认识到的更加多样化。当肾小球肾炎表现为X连锁遗传模式时，应考虑COL 4A 5突变分析，即使其表现与Alport综合征不同。
We report a novel COL4A5 mutation causing rapid progression to end stage renal disease in males despite the absence of clinical and biopsy findings associated with Alport syndrome. Affected males had proteinuria, variable hematuria, early progression to end stage renal disease; and renal biopsy findings which included global and segmental glomerulosclerosis, mesangial hypercellularity and basement membrane immune complex deposition. Exon sequencing of the COL4A5 locus identified a thymine to guanine transversion at nucleotide 665, resulting in a phenylalanine to cysteine missense mutation at codon 222. This mutation was confirmed in 4 affected males and 4 female obligate carriers, but was absent in 6 asymptomatic male family members and 198 unrelated individuals. α5(IV) collagen staining in renal biopsies from affected males was normal. The phenylalanine at position 222 is 100% conserved among vertebrates. This is the first description of a mutation in a non-collagenous interruption associated with severe renal disease, providing evidence for the importance of this structural motif. The range of phenotypes associated with COL4A5 mutations is more diverse than previously realized. COL4A5 mutation analysis should be considered when glomerulonephritis presents in an X-linked inheritance pattern, even with a distinct presentation from Alport syndrome.
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影响因子：
6
作者：
Harvey, SJ;Zheng, KQ;Thorner, PS
通讯作者：
Thorner, PS
影响因子：
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